Tatsuya Okuzumi

Efficient solid-phase synthesis of quinazoline-2,4-diones with various substituents on aromatic rings

We have developed a method for the solid-phase synthesis of quinazoline-2,4-diones with various substituents on the aromatic ring. Although there have been numerous reports of the solid-phase synthesis of quinazoline-2,4-diones, they were not applicable to the synthesis of the quinazoline-2,4-diones with electron-withdrawing substituents on the aromatic ring. Considering the poor nucleophilicity of the amino group of anthranilic acids, coupling of anthranilic acids to solid-supported amines was investigated without protecting the amino group. Various anthranilamides were prepared using anthranilic acids with electron-withdrawing substituents because a wide range of anthranilic acids are commercially available. These anthranilamides were successfully cyclized with carbonyldiimidazole to give quinazoline-2,4-diones with high purity.

Solid-phase synthesis of 2-substituted-3-(substituted sulfanyl)-1,2,4-benzothiadiazine 1,1-dioxide library

Abstract The first solid-phase synthesis of 2-substituted-3-(substituted sulfanyl)-1,2,4-benzothiadiazine 1,1-dioxides has been developed. Synthesis of the title compounds was achieved as follows: (1) sulfonylation of solid-supported primary amines with 2-nitrobenzenesulfonylchlorides, (2) reduction of the nitro group, (3) cyclization with thiocarbonyldiimidazole (formation of thiourea), (4) S-alkylation or S-arylation of the thiourea. In addition to the excellent purity of the product, a large-size library can be synthesized with the method as this synthesis includes three diversity points.